Biomarker alterations with metronomic use of low-dose zoledronic acid for breast cancer patients with bone metastases and potent

Primary tabs

field_vote: 
Average: 9 (1 vote)
Publication type: 
Number of included patients: 
References: 
Therapeutic intervention: 
Disease(s): 
Therapeutic Substance(s): 

Breast Cancer Res Treat. 2010 Sep 30. [Epub ahead of print]
Biomarker
alterations with metronomic use of low-dose zoledronic acid for breast
cancer patients with bone metastases and potential clinical
significance.
Zhao X, Xu X, Guo L, Ragaz J, Guo H, Wu J, Shao Z, Zhu J, Guo X, Chen J, Zhu B, Wang Z, Hu X.
Department of Medical Oncology, Fudan University Cancer Hospital, No. 270, Dong An Road, Shanghai, 200032, China.

Abstract
Zoledronic
acid has direct and indirect antitumor effects. However, the optimal
regimen for breast cancer patients remains to be determined. This study
aimed to compare biomarker changes between a weekly low dose (metronomic
arm) and a conventional dosage of zoledronic acid (conventional arm),
and to explore correlations between biomarkers and progression-free
survival (PFS). Sixty breast cancer patients with bone metastases were
randomized to receive either zoledronic acid 1 mg IV weekly for 4 doses
or a single dose of zoledronic acid 4 mg IV. Administration of other
treatments was delayed for 1 month. Serial blood samples were collected
on days 1, 15, 29, and at 3 months. Serum VEGF alteration was the
primary endpoint. Compared to the conventional arm, the metronomic arm
resulted in a significantly greater reduction in serum levels of VEGF
and N-telopeptide of type I collagen (NTx) over time during the first
month of treatment. Serum CA 15-3 level stabilized over time in the
metronomic arm, but increased in the conventional arm. Independent
prognostic factors for PFS included chemotherapy received (HR, 8.042;
P = 0.000), estrogen receptor status (HR, 2.837; P = 0.020), VEGF levels
at 3 months after intervention (HR, 2.026; P = 0.045), and baseline NTx
(HR, 1.051; P = 0.001). Metronomic low-dose zoledronic acid is more
effective than the conventional regimen and generates sustained
reductions in circulating VEGF and NTx levels, as well as stabilization
of serum CA 15-3 levels (ClinicalTrials.gov number, NCT00524849).